Lymphoma: From Diagnosis to New Treatments, Every Patient Has a Different Journey

A diagnosis of lymphoma can bring fear and uncertainty. Yet the term encompasses a wide range of diseases, some slow-growing and others more rapidly progressing, each with different treatment approaches and outcomes. As advances in genetics and immunotherapy create new opportunities, one potentially surprising concept is becoming increasingly important: in some cases, waiting before starting treatment may be the most appropriate approach.

Professor Antonio Cuneo, Director of the Hematology Unit at Ferrara University Hospital, explains how the diagnosis and treatment of these diseases are evolving. He discusses the differences between lymphoma types, the signs and symptoms that warrant medical attention, and emerging treatment options, from CAR T-cell therapy to bispecific antibodies.

Not All Lymphomas Are the Same

Lymphoma is often thought of as a single disease. In fact, the term refers to a broad group of cancers that arise from cells of the immune system, particularly lymphocytes.

“The first major distinction is between Hodgkin lymphoma and non-Hodgkin lymphomas. Hodgkin lymphoma is a disease with well-defined biological characteristics. It frequently affects young people and, today, has a high likelihood of cure in the vast majority of cases,” Professor Cuneo explains.

Non-Hodgkin lymphomas, by contrast, comprise numerous diseases that differ in their biological behavior, rate of growth, and response to treatment.

Some are described as indolent: they progress slowly, can be controlled for many years, and, under certain circumstances, do not require immediate treatment. Others are classified as aggressive because they grow more rapidly and require prompt treatment.

However, Cuneo emphasizes an important distinction concerning the word aggressive.

“It is important to stress that aggressive does not mean ‘severe,’ and certainly does not mean ‘unlikely to respond to treatment.’”

The term describes how quickly the disease grows, rather than necessarily indicating its likelihood of being cured. Indeed, the professor adds: “The vast majority of rapidly growing lymphomas are particularly sensitive to treatment and can be cured.”

Prognosis therefore depends not only on the type of lymphoma, but also on the extent of the disease, its biological characteristics, and the patient’s age and overall health.

Two patients with seemingly similar diagnoses may follow very different treatment pathways and have very different outcomes.

Enlarged Lymph Nodes: When Should You Seek Medical Advice?

An enlarged lymph node is one of the signs that most often causes concern. But how worrying should it be?

“In the vast majority of cases, having an enlarged lymph node does not mean having lymphoma. Lymph nodes are part of our immune system and can become enlarged for many reasons, particularly in response to infection or inflammation.”

Professor Cuneo advises against unnecessary alarm, while emphasizing that persistent changes should not be overlooked.

Medical advice should be sought if a lymph node remains enlarged for several weeks without an obvious cause, continues to grow, or has unusual features, such as a particularly hard consistency or limited mobility. Enlarged lymph nodes in less common locations, such as above the collarbone, also warrant assessment.

Certain general symptoms may also require further investigation: persistent unexplained fever, drenching night sweats, significant unintentional weight loss, persistent itching, or marked unexplained fatigue.

“None of these symptoms, taken individually, necessarily indicates the presence of lymphoma.”

The message is to remain attentive without becoming unduly alarmed: symptoms should not automatically be interpreted as signs of cancer, but persistent or worsening changes should not be ignored.

Genetics and Lymphoma: Towards More Personalized Treatment

In recent years, the study of the genetic and molecular characteristics of cancer has profoundly changed our understanding and treatment of many hematological malignancies.

“Today, we no longer simply examine lymphoma cells under a microscope. We can also investigate their genetic and molecular characteristics, looking for alterations that have contributed to malignant transformation and influence how the disease behaves,” Cuneo explains.

These analyses help identify the type of lymphoma more precisely and, in some cases, reveal features associated with more or less aggressive disease.

However, the professor highlights an important point, particularly to avoid unnecessary concern among patients and their families.

“Finding a genetic alteration in lymphoma cells does not necessarily mean that the disease is hereditary or that it can be passed on to your children.”

In most cases, these alterations are acquired by cancer cells during a person’s lifetime. They are present in the tumor cells rather than throughout the body. An inherited predisposition may exist in particular circumstances and requires specific assessment.

Above all, understanding the molecular characteristics of the disease opens up new treatment possibilities.

“Perhaps the most interesting aspect is that some alterations can serve as therapeutic targets. If we identify a particular feature of the cancer cell, we can, in some cases, use drugs designed specifically to target that mechanism.”

Not every genetic alteration directly changes the choice of treatment. Nevertheless, the direction of research is clear: developing treatments that are increasingly tailored to the biology of each patient’s lymphoma.

Active Surveillance: When Deferring Treatment Is the Best Approach

Receiving a cancer diagnosis and being told that treatment does not need to begin immediately may seem contradictory.

Yet, for some slow-growing lymphomas, this is an established management strategy.

“It may seem counterintuitive to receive a cancer diagnosis and be told that, at least initially, treatment is not necessary. Yet, for certain slow-growing lymphomas, this is a well-established strategy that we call ‘active surveillance’ or ‘watch and wait.’”

Active surveillance is used when the disease is not causing symptoms, is not impairing organ function, and has features consistent with a slow-growing course.

Under these circumstances, starting treatment immediately does not necessarily provide an advantage over waiting until specific clinical indications arise.

Cuneo also highlights a particularly important point: some patients with indolent lymphoma may not require treatment for many years, and some may never need it during their lifetime.

Starting treatment earlier would therefore expose them to potential side effects without providing a meaningful benefit.

“‘Waiting,’ of course, does not mean doing nothing. Patients are monitored regularly through clinical assessments and appropriate investigations, and treatment is started if and when specific clinical indications arise.”

This approach requires regular monitoring and a trusting relationship with the treating team, while helping patients avoid unnecessary treatment.

As the professor puts it, “in oncology, treating earlier does not always mean treating better.”

CAR T-Cell Therapy and Bispecific Antibodies: New Frontiers in Lymphoma Treatment

Among the advances transforming the treatment of several types of lymphoma, therapies that harness the immune system to recognize and attack cancer cells are playing an increasingly important role.

“CAR T-cell therapy and bispecific antibodies represent one of the most important developments in the treatment of many B-cell lymphomas in recent years,” Cuneo says.

These approaches are used across several lymphoma subtypes, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, high-grade B-cell lymphomas, follicular lymphoma, and mantle cell lymphoma.

Although both approaches aim to generate an immune response against cancer, CAR T-cell therapy and bispecific antibodies work in different ways.

CAR T-cell therapy uses the patient’s own immune cells, which are genetically modified in a laboratory.

“With CAR T-cell therapy, we collect some of the patient’s T lymphocytes, which are cells of the immune system, and modify them in the laboratory so that they can recognize lymphoma cells with a high degree of specificity.”

Once modified, these cells are infused back into the patient, where they can recognize and attack cancer cells.

“We can think of them as immune cells that have been trained to recognize and destroy lymphoma cells,” the professor explains.

Bispecific antibodies, by contrast, bring cancer cells and T lymphocytes into close contact.

“These drugs can bind simultaneously to a lymphoma cell and a T lymphocyte, bringing them into physical contact and thereby promoting an immune attack against the cancer.”

These therapies are particularly valuable for patients whose disease has not responded adequately to previous treatments.

In some cases, the two approaches can also be used sequentially, with the most appropriate treatment pathway determined by the characteristics of the disease and the patient’s clinical condition.

However, these therapies are not without risks. They require careful patient selection and must be administered in centers with specific expertise.

“The most important point, however, is that we can now offer new possibilities even in situations where, until just a few years ago, treatment options were very limited.”

The Value of Research and Access to New Treatments

Progress in lymphoma care is not only about treatment effectiveness. It is also about ensuring that patients who need these treatments can access them.

New immunotherapies represent a significant advance, but they are also expensive and require highly specialized facilities.

In this context, Professor Cuneo emphasizes the fundamental role of the public healthcare system.

“Only a national health service can guarantee access to these very expensive therapies for all citizens, regardless of their income.”

His observation extends the discussion beyond scientific research to the question of equitable access to care.

From increasingly precise diagnosis and personalized treatment to active surveillance and new immunotherapies, lymphoma care is undergoing a significant transformation.

The central message emerging from Professor Antonio Cuneo’s words is that lymphoma is not a single disease, and there can therefore be no single treatment pathway suitable for everyone. Understanding the characteristics of the disease, choosing the appropriate time to intervene, and making use of new treatment options all contribute to increasingly targeted care, in which each decision is tailored to the individual and their specific clinical circumstances.